CIRCULATORY EFFECTS OF ENDOTHELIN IN NEWBORN PIGLETS

Endothelin, a recently described endothelial cell-derived peptide, produces pulmonary and coronary vasoconstriction in mature animals. We investigated the acute hemodynamic effects of porcine endothelin in 14 anesthetized open-chest newborn piglets during normoxia (Pa(o)2 = 102 +/- 5 mmHg) and hypoxia (fractional inspired O2 concentration = 0.12 x 15 min, Pa(o)2 = 31 +/- 1 mmHg). Six of these animals were pretreated with indomethacin, a cyclooxygenase inhibitor. Low-dose (100 pmol/kg) intravenous bolus injection of endothelin decreased pulmonary vascular resistance index (PVRI) (42 +/- 6 to 16 +/- 4 mmHg.1(-1).min.kg, P < 0.01) and increased coronary blood flow (CBF) (17 +/- 2%, P < 0.01); cardiac index (CI) and coronary vascular resistance were unaffected. The pulmonary and coronary responses to endothelin were preserved during hypoxia: PVRI fell (160 +/- 22 to 83 +/- 13 mmHg.1(-1).min.kg, P < 0.05) and CBF rose (35 +/- 11%, P < 0.05). Low-dose endothelin moderately increased mean arterial pressure (61 +/- 3 to 75 +/- 6 mmHg, P < 0.05) and systemic vascular resistance index (SVRI) (375 +/- 23 to 491 +/- 41 mmHg.1(-1).min.kg, P < 0.01). High-dose (1,000 pmol/kg) endothelin mildly decreased PVRI (51 +/- 7 to 35 +/- 12, NS), moderately increased SVRI (375 +/- 45 to 594 +/- 95 mmHg.1(-1).min.kg, P < 0.05), and markedly diminished CBF (-54 +/- 6%, P < 0.01). Left ventricular end-diastolic pressure rose (9 +/- 1 to 17 +/- 3 mmHg, P < 0.05) and shortening fraction fell (15.9 +/- 1.4 to 11.1 +/- 2.0%, P < 0.05) in response to high-dose endothelin. CI did not change. Pretreatment with indomethacin did not significantly alter either the pulmonary or coronary vascular responses to low-dose endothelin but completely prevented high-dose endothelin-induced coronary vasoconstriction and left ventricular dysfunction. The results indicate that cyclooxygenase products are unlikely to exclusively mediate endothelin-induced vasodilation but may play a role in endothelin-induced coronary vasoconstriction in newborn piglets.